BioPAX pathway converted from "PIP3 recruits AKT to the membrane" in the Reactome database. LEFT-TO-RIGHT PIP3 recruits AKT to the membrane This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome AKT Reactome DB_ID: 10691044 AKT1 Q8INB9 Reactome DB_ID: 10691040 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q8INB9 Akt1 Akt1 CG4006 FUNCTION Serine/threonine kinase involved in various developmental processes (PubMed:9601646, PubMed:10587646, PubMed:10962553, PubMed:11740943, PubMed:12172554, PubMed:11872800, PubMed:14525946, PubMed:12893776, PubMed:15466161, PubMed:15712201). During early embryogenesis, acts as a survival protein (PubMed:9601646, PubMed:10962553). During mid-embryogenesis, phosphorylates and activates trh, a transcription factor required for tracheal cell fate determination (PubMed:11740943). Also regulates tracheal cell migration (PubMed:11740943, PubMed:14525946). Later in development, acts downstream of PI3K and Pk61C/PDK1 in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and antagonizing FOXO transcription factor (PubMed:10587646, PubMed:10962553, PubMed:11752451, PubMed:12893776, PubMed:25329475, PubMed:29025897, PubMed:24603715). Controls follicle cell size during oogenesis (PubMed:15712201). May also stimulate cell growth by phosphorylating Gig/Tsc2 and inactivating the Tsc complex (PubMed:12172554, PubMed:15466161). Dephosphorylation of 'Ser-586' by Phlpp triggers apoptosis and suppression of tumor growth (PubMed:10962553).SUBUNIT Interacts with trbl.TISSUE SPECIFICITY Ubiquitously expressed. Present in ovary, where it is concentrated at the basal side of follicle cells.DEVELOPMENTAL STAGE Expressed both maternally and zygotically. Strongly expressed in embryo and pupa. Weakly expressed in larva. Mildly expressed in adult.DOMAIN Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.PTM Phosphorylated and activated by Pk61C/PDK1 (PubMed:11344272). Phosphorylated on Ser-586 by the TORC2 complex (PubMed:10962553, PubMed:15718470, PubMed:22493059).DISRUPTION PHENOTYPE Death at the first instar larval stage (PubMed:9601646). Conditional RNAi-mediated knockdown in the female germline reduces ovary size (PubMed:24786828). RNAi-mediated knockdown in both larval salivary glands and fat body, results in small salivary glands displaying ectopic lipid storage and reduced expression of CdsA (PubMed:24603715).SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. Drosophila melanogaster NCBI Taxonomy 7227 UniProt Q8INB9 1 EQUAL 480 EQUAL Reactome Database ID Release 83 10691040 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10691040 Reactome R-DME-58252 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-58252.1 Reactome http://www.reactome.org AKT3 Q8INB9 Reactome DB_ID: 10691042 1 EQUAL 479 EQUAL Reactome Database ID Release 83 10691042 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10691042 Reactome R-DME-2976007 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-2976007.1 AKT2 Q8INB9 Reactome DB_ID: 10677719 1 EQUAL 481 EQUAL Reactome Database ID Release 83 10677719 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10677719 Reactome R-DME-49859 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-49859.1 Reactome Database ID Release 83 10691044 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10691044 Reactome R-DME-202088 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-202088.1 PIP3 PI(3,4,5)P3 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate Phosphatidylinositol-3,4,5-trisphosphate Reactome DB_ID: 179838 plasma membrane GENE ONTOLOGY GO:0005886 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate(7-) [ChEBI:57836] 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate(7-) 2,3-bis(alkanoyloxy)propyl (1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonatooxy)cyclohexyl phosphate a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) ChEBI CHEBI:57836 Reactome Database ID Release 83 179838 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179838 Reactome R-ALL-179838 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-179838.4 COMPOUND C05981 additional information MI MI:0361 AKT:PIP3 Reactome DB_ID: 10684696 Converted from EntitySet in Reactome AKT Reactome DB_ID: 10684694 AKT1 Q8INB9 Reactome DB_ID: 10684688 1 EQUAL 480 EQUAL Reactome Database ID Release 83 10684688 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10684688 Reactome R-DME-199416 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-199416.1 AKT2 Q8INB9 Reactome DB_ID: 10684690 1 EQUAL 481 EQUAL Reactome Database ID Release 83 10684690 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10684690 Reactome R-DME-202053 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-202053.1 AKT3 Q8INB9 Reactome DB_ID: 10684692 1 EQUAL 479 EQUAL Reactome Database ID Release 83 10684692 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10684692 Reactome R-DME-2976006 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-2976006.1 Reactome Database ID Release 83 10684694 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10684694 Reactome R-DME-202052 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-202052.1 1 1 Reactome Database ID Release 83 10684696 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10684696 Reactome R-DME-2317329 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-2317329.1 Reactome Database ID Release 83 10713463 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10713463 Reactome R-DME-2317332 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-2317332.1 GENE ONTOLOGY GO:0032148 gene ontology term for cellular process MI MI:0359 PIP3 generated by PI3K recruits AKT (also known as protein kinase B) to the membrane, through its PH (pleckstrin-homology) domains. The binding of PIP3 to the PH domain of AKT is the rate-limiting step in AKT activation (Scheid et al. 2002). In mammals there are three AKT isoforms (AKT1-3) encoded by three separate genes. The three isoforms share a high degree of amino acid identity and have indistinguishable substrate specificity in vitro. However, isoform-preferred substrates in vivo cannot be ruled out. The relative expression of the three isoforms differs in different mammalian tissues: AKT1 is the predominant isoform in the majority of tissues, AKT2 is the predominant isoform in insulin-responsive tissues, and AKT3 is the predominant isoform in brain and testes. All 3 isoforms are expressed in human and mouse platelets (Yin et al. 2008; O'Brien et al. 2008). Note: all data in the pathway refer to AKT1, which is the most studied. 2008 The role of Akt3 in Platelet Activation O'Brien, K Stojanovic, A Hay, N Du, X Arteriosclerosis, Thrombosis, and Vascular Biology 28:e162 17914025 Pubmed 2008 The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activation Yin, H Stojanovic, A Hay, N Du, X Blood 111:658-65 12167717 Pubmed 2002 Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B Scheid, MP Marignani, PA Woodgett, JR Mol Cell Biol 22:6247-60 inferred from electronic annotation EVIDENCE CODE ECO:0000203